Cargando…

Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype–phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To dete...

Descripción completa

Detalles Bibliográficos
Autores principales: Schuldt, Maike, van Driel, Beau, Algül, Sila, Parbhudayal, Rahana Y., Barge-Schaapveld, Daniela Q. C. M., Güçlü, Ahmet, Jansen, Mark, Michels, Michelle, Baas, Annette F., van de Wiel, Mark A., Nieuwdorp, Max, Levin, Evgeni, Germans, Tjeerd, Jans, Judith J. M., van der Velden, Jolanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616419/
https://www.ncbi.nlm.nih.gov/pubmed/34831173
http://dx.doi.org/10.3390/cells10112950
_version_ 1784604343769497600
author Schuldt, Maike
van Driel, Beau
Algül, Sila
Parbhudayal, Rahana Y.
Barge-Schaapveld, Daniela Q. C. M.
Güçlü, Ahmet
Jansen, Mark
Michels, Michelle
Baas, Annette F.
van de Wiel, Mark A.
Nieuwdorp, Max
Levin, Evgeni
Germans, Tjeerd
Jans, Judith J. M.
van der Velden, Jolanda
author_facet Schuldt, Maike
van Driel, Beau
Algül, Sila
Parbhudayal, Rahana Y.
Barge-Schaapveld, Daniela Q. C. M.
Güçlü, Ahmet
Jansen, Mark
Michels, Michelle
Baas, Annette F.
van de Wiel, Mark A.
Nieuwdorp, Max
Levin, Evgeni
Germans, Tjeerd
Jans, Judith J. M.
van der Velden, Jolanda
author_sort Schuldt, Maike
collection PubMed
description Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype–phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics.
format Online
Article
Text
id pubmed-8616419
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86164192021-11-26 Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy Schuldt, Maike van Driel, Beau Algül, Sila Parbhudayal, Rahana Y. Barge-Schaapveld, Daniela Q. C. M. Güçlü, Ahmet Jansen, Mark Michels, Michelle Baas, Annette F. van de Wiel, Mark A. Nieuwdorp, Max Levin, Evgeni Germans, Tjeerd Jans, Judith J. M. van der Velden, Jolanda Cells Article Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype–phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics. MDPI 2021-10-29 /pmc/articles/PMC8616419/ /pubmed/34831173 http://dx.doi.org/10.3390/cells10112950 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schuldt, Maike
van Driel, Beau
Algül, Sila
Parbhudayal, Rahana Y.
Barge-Schaapveld, Daniela Q. C. M.
Güçlü, Ahmet
Jansen, Mark
Michels, Michelle
Baas, Annette F.
van de Wiel, Mark A.
Nieuwdorp, Max
Levin, Evgeni
Germans, Tjeerd
Jans, Judith J. M.
van der Velden, Jolanda
Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy
title Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy
title_full Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy
title_fullStr Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy
title_full_unstemmed Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy
title_short Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy
title_sort distinct metabolomic signatures in preclinical and obstructive hypertrophic cardiomyopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616419/
https://www.ncbi.nlm.nih.gov/pubmed/34831173
http://dx.doi.org/10.3390/cells10112950
work_keys_str_mv AT schuldtmaike distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT vandrielbeau distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT algulsila distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT parbhudayalrahanay distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT bargeschaapvelddanielaqcm distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT gucluahmet distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT jansenmark distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT michelsmichelle distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT baasannettef distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT vandewielmarka distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT nieuwdorpmax distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT levinevgeni distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT germanstjeerd distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT jansjudithjm distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy
AT vanderveldenjolanda distinctmetabolomicsignaturesinpreclinicalandobstructivehypertrophiccardiomyopathy